The previously received results of individual processes of hydrodynamic and alkaline disintegration were decisive significant for the conducted research task. The combination of hydrodynamic cavitation (30 minutes duration of the process) and alkaline (pH ≈ 9) to the destruction of activated sludge caused a significant release of organic matter about 1383 mg/dm3 in comparing to individual processes. Such increase in the SCOD value resulted in a significant growth the efficiency of biogas yield in a two-stage mesophilic-thermophilic processes. The increase in yield was from 26 to 38% depending on the volume of disintegrated sludge. The effect of the two-stage fermentation resulted activated sludge hygienisation. The microbiological analysis of the influence of the fermentation with the different volume of hybrid disintegrated sludge was based on microbiological indicators: Salmonella spp. and coliphages. The obtained results prove the effectiveness of the two-stage digestion process compared to single mesophilic fermentation which not always completely eliminates the above indicators.